Threatening or aversive experiences can produce enduring fear memories that last a lifetime. Indeed, rather than normal forgetting, fear memories may incubate becoming more intense as time passes. In addition, the triggers for old fear memories become less specific; as time passes fear becomes increasingly generalized to conditions that differ from the original context of the trauma. These three attributes of fear memory (enduring, incubating and generalizing) are no doubt major contributors to the fact that anxiety disorders are so prevalent in society and so debilitating to the individuals that suffer from them. The research proposed here is directed at the question of how the brain translates an experience into a permanent memory that increases in intensity (incubation) and becomes less specific over time (generalization). Our hypothesis is that, the enduring, incubating and generalizing attributes of fear memory require coordinated activity in several neural structures and it is this coordinated activity that gives traumatic memories these attributes. We propose 3 aims to answer the questions raised by this hypothesis: 1) Where in the overall fear network must activity occur to establish enduring, incubating and generalizing fear memory? To achieve this we will inactivate connections between the brain structures that comprise the network and determine which of these projections contribute to enduring fear. 2) When, in relationship to the threatening experience, must this activity occur? To answer this question we will inactivate the relevant pathways at specific times in relation to the trauma to determine if activity during acquisition, retention or recall is most important for these features of fear memory. 3) What is the nature of the activity that leads to the expression of the 3 attributes of enduring memory? We will image network activity at the single neuron level to determine what patterns of activity give rise to these powerful attributes of fear. PUBLIC HEALTH RELEVANCE: Anxiety disorders are very common and very debilitating to both the individuals, and their families, that suffer from them. The debilitation arises because fear memories last a lifetime, while they increase in intensity and are triggered by less specific events. This grant seeks to determine how the brain creates memories with these attributes.